Although the application is listed as an R-01, the work described in the application is a continuation of a previous R-01 that became a subproject in a Program Project Grant at the Mayo Clinic and subsequently moved to the University of Vermont as Project 1 in the Vermont Specialized Center for Research in Thrombosis. Dr. Mann's specific aims are to: quantitate protein-protein interactions involved in prothrombinase and other vitamin K dependent complexes; to evaluate the tissue factor (TF)/VIIa complex in terms of physical and kinetic interactions; to evaluate factor Xa/thrombomodulin interactions; to study surface dependent coagulation reactions using total internal reflectance fluorescence (TIRF); and to image coagulation enzymes adn complexes using high resolution electron microscopy and crystallography. The applicant described in detail the reagents and methods to be used; the experimental design and anticipated results. Much of the application is based on the hypothesis that the coagulation reactions on membranes are examples of a channeled enzymatic process in which the products of one enzymatic process rearranges on the membrane surface to form a succeeding enzyme complex rather than being transported through solution.